Chemical analyser, method for sample-based analysis, device for handling cuvettes, and loading method

ABSTRACT

With the aid of the invention, a chemical analyser, a method for sample-based analysis, a device for handling cuvettes, and a loading method are provided. The chemical analyser ( 1 ) according to the invention comprises a rotatable incubator ( 20 ), in which there are openings ( 21 ) for receiving cuvettes ( 70 ), and analysis means ( 60 ) arranged around the incubator ( 20 ), as well as a loading device ( 40 ) for loading cuvettes ( 70 ) into the openings ( 21 ). The loading device ( 40 ) of the analyser ( 1 ) comprises a feed funnel ( 30 ), which is arranged to bend a straight cuvette ( 70 ) to fit the opening ( 21 ), and a ram ( 41 ), which is arranged to load a cuvette ( 70 ) into an opening ( 21 ) in the incubator ( 20 ) through the feed funnel ( 30 ).

The present invention relates to automatic devices and methods intendedfor chemical analyses. In particular, the invention relates to theanalysis in automatic analysers of solutions formed by samples andreagent substances. More specifically, the invention relates to ananalyser and method according to the preambles of claims 1, 10, 13, and20.

Samples have traditionally been examined using analysers, which havechanged from manually operated test devices to automated multi-purposedevices. Present analysers can perform several different tests and canbe used to achieve comparatively short throughput times, as well as goodproductivity with low personnel costs. In conventional automaticanalysers, a circular rotatable incubator is traditionally used, on theouter circumference of which openings are made to receive cuvettes. Thecuvettes placed in the incubators are usually reaction vessels, intowhich the analyser doses the substance to be analysed and the reagentsubstances causing reactions.

A move has taken place from the individual reaction vessels oftraditional incubators to cuvettes, which contain several reactionvessels, which has increased the efficiency of analysers. For example,publication U.S. Pat. No. 5,104,808 A discloses an automatic incubatorhaving curvaceous openings, to at least one of which has a cluster forreaction vessels, from which cluster the sample can be analysedoptically after it has been mixed with reagent substances. Reactionvessels having elastic bindings, on the other hand, are known frompublication U.S. Pat. No. 5,720,406 A, which discloses a principle ofbending reaction vessels to curvaceous openings without analysing thesamples while in a reaction vessel. Furthermore, publication EP 0577822B1 discloses a method of cutting a portion, having at least twocuvettes, of an elastic cuvette belt and transporting the portion toopenings on the perimeter of a rotatable carousel. Publication U.S. Pat.No. 5,096,672 A also discloses a cuvette row having a plurality ofcuvettes, which cuvette row can be shaped in a curved form.

A problem with the type of device described has been the low degree ofmodularity of the analysers and the cuvettes they use. In analysersdesigned for present systems for large numbers of analyses, there arelarge incubators, into which a significant number of cuvettes can beloaded. However, these cuvettes cannot be utilized in analysers intendedfor smaller numbers of samples, so that a special type of cuvette isrequired for each size of device, which leads to additional purchase andstorage costs.

The present invention is intended to eliminate at least some of thedefects of the prior art and for this purpose create a chemical analyserand analysis method, in connection with which it is possible to usestandardized bendable cuvettes, which can receive several samples.

The chemical analyser according to the invention comprises a rotatableincubator, which is equipped with openings to receive the cuvettesloaded into it. In the analyser, there are, in addition, analysis meansarranged around the incubator and a loading device for loading thecuvettes into the openings, which are curved. For its part, theanalyser-loading device comprises a feed funnel, by means of which astraight cuvette is bent to fit into the curved openings of theincubator, and a ram, by means of which the cuvettes are loaded into theopenings of the incubator, through the feed funnel.

More specifically, the chemical analyser according to the invention ischaracterized by what is stated in the characterizing portion of claim1.

In the method according to the invention for analysing samples, theanalysis sequence is defined sample-specifically, after which a cuvette,which comprises at least two reaction vessels, into which the sample andthe reagent are dosed, is loaded into an opening in the incubatorthrough a bending feed funnel, which bends the cuvette to fit saidopening. In the analysis of the sample, at least one sample in thecuvette is analysed, the sample being in a reaction vessel.

More specifically, the method according to the invention for analysingsample is characterized by what is stated in the characterizing portionof claim 10.

The device according to the invention for handling cuvettes comprises arotatable incubator and a loading device. In the incubator, there is atleast one curved opening for receiving and transporting a cuvette. Theloading device comprises a loading track for storing unloaded straightcuvettes and transporting them to the incubator, as well as a ram, whichis arranged to press the cuvette at the incubator end of the loadingtrack into an opening in the incubator. The loading device alsocomprises a feed funnel, which is arranged to receive the straightcuvette pressed by the ram and to bend it to allow it to be pushed intothe curved opening of the incubator.

More specifically, the device according to the invention for handlingcuvettes is characterized by what is stated in the characterizingportion of claim 13.

In the loading method according to the invention for loading a cuvetteinto an opening in an incubator, the cuvette is transported to thelocation of the opening in the incubator and loading into the opening inthe incubator by moving the ram. During loading, the cuvette is shapedto fit the opening in the incubator by using the ram to load it throughthe curved feed funnel.

More specifically, the loading method according to the invention ischaracterized by what is stated in the characterizing portion of claim20.

Considerable advantages are gained with the aid of the invention. Thanksto the feed funnel of the analyser, analysers of different sizes can usesame-size standard cuvettes, which contain several sample vessels.Analysers suitable for standardized cuvettes receiving many samplespermit volume benefits when purchasing cuvettes. The storage of thecuvettes too is cheap, as only one type of cuvette is required, so thatadditional resources are not needed to maintain the articles. Inaddition, because the cuvette is straight, it is easier to store than,for example, a curved cuvette.

In the following, embodiments of the invention are examined in greaterdetail with reference to the accompanying drawings.

FIG. 1 shows a top view of the analyser according to the invention.

FIG. 2 shows a perspective view of the analyser of FIG. 1.

FIG. 3 shows the feed funnel of FIGS. 1 and 2.

FIG. 4 shows the difference between sample-based and test-batch-basedanalysis.

As can be seen from FIGS. 1 and 2, the analyser 1 according to theinvention comprises a heated incubator 20, on the outer edge of whichopenings 21 are made, to receive cuvettes. The incubator according tothe invention is particularly suited for use with cuvettes that are madefrom a sufficiently elastic and clear material. The elasticity permitselastic bending of the connecting web part of the cuvettes relative toits longest side, while the clearness permits the sample contained inthe cuvette to be analysed through the wall of the cuvette, so that itis not necessary to remove the sample from the cuvette during analysis.According to the invention, a cuvette 70, which consists of severalreaction vessels and web parts connecting them, is loaded into theopenings 21 of the incubator 20. The cuvette 70 can contain, forexample, 10 reaction vessels next to each other, in such a way thattheir connecting web parts are parallel to each other, in which case theorientation of the cuvette 70 is straight and it can receive 10different samples. The outermost reaction vessels of a particularlyadvantageous cuvette 70 are, in addition, equipped with flexibletongues, with the aid of which the cuvette 70 can be bent into a curve,without immediately compressing the outermost sample vessels. Cuvetteslike those described, which are especially well suited to the invention,are disclosed in Finnish patent application 20085509.

The circular incubator 20 according to the invention is mounted onbearings in the centre and rotation means (not shown) are fitted to it,with the aid of which the incubator 20 can be rotated to the desiredextent in the desired direction. The rotation means can comprise, forexample, a servomotor, which has excellent positioning precision, butthe price of which is extremely high. Indeed, the power transmission ofthe incubator 20 can be implemented with sufficient precision by fittingit directly to the shaft of a cost-effective stepped motor, which issufficiently precise for the purpose, so that there are only theessential number of moving parts, and thus the minimum number of causesof play, in the transmission. In the power transmission of the rotationmeans, it is essential that the rotational speed and positioningprecision are sufficiently great and that accelerations of the incubator20 are controlled and soft.

The analyser 1 also comprises a loading device 40 fitted in connectionwith the incubator 20. The loading device 40 comprises means fordelivering the cuvettes 70 to the incubator 20. The loading device 40comprises a loading track 50, along which the cuvettes 70 are broughtfor loading into the opening 21 of the incubator 20. At its simplest,the loading track 50 is a trough with a U-shaped cross-section, thebottom of which is dimensioned to be as wide as the lower edge of thecuvette 70 being loaded and that the vertical edges of the trough areessentially higher than the cuvette 70. Thus, the cuvette 70 can betransported on the loading track 50 from its lugs, in such a way thatthe lugs of the cuvette 70 are set on top of the vertical edges of theloading track 50, thus keeping the lower edges of the sample vessel at adistance from the bottom of the loading track 50. The gap remainingbetween the lower edge of the cuvette 70 and the bottom of the loadingtrack 50 ensures that the lower edge of the cuvette 70 does not dragalong the bottom of the loading track 50, and thus does not cause noiseor scratching. Because the cuvettes 70 transported on the loading track50 are straight, their transportation is easy and they will not easilyjam when being pushed. The cuvettes 70 are transported by a pusher (notshown), which pushes a row of cuvettes 70 suspended by their lugsforwards to the incubator 20. The pusher can be, for example, a simplepneumatic cylinder, which can be controlled by remote commands.Alternatively, the loading track 50 can be sloping, in which case thecuvettes 50 move along the track by gravitational acceleration, so thatthere will always be a cuvette 70 at the feed funnel 30, ready to beloaded. However, more than one cuvette 70 cannot be in the feed funnel30 at one time, because the shaft of the ram 41 prevents the nextcuvette 70 from entering the funnel during the loading movement.

The feed funnel 30, which is part of the loading device 40 and throughwhich the cuvettes 70 are fed to the openings 21 of the incubator, isfitted to the end of the loading track 50 next to the incubator 20. Inloading, the loading device's 40 ram 41 is used, the lower edge of whichis arranged to press the cuvette 70 with a single movement into the feedfunnel 30, in which it is arranged to be shaped to fit the opening 21.The curvature of the opening 21 conforms to the curvature of the outercircumference of incubator 20. Due to the flexibility of the cuvette 70,it can be used for incubators 20 of several different sizes, which havedifferent radii of curvature. In this connection, the term straightrefers to a cuvette, the curvature of which has not been changed bybending the cuvette. Correspondingly, the term a curved cuvette refersto a cuvette, the curvature of which has been changed by bending thecuvette.

As can be seen from FIG. 3, the feed funnel 30 is shaped in such a waythat when travelling through it, a cuvette 70 takes a curved shapesuitable for the opening 21, by means of a single movement of the ram41. The side 31 of the feed funnel 30 receiving the cuvette 70 isconvex, when examined from the direction of arrival of the cuvette 70,so that, when pressed against it, the cuvette 70 bends to conform to thecircumference of the incubator 20. The feed funnel 30 is dimensioned insuch a way that the curvature of its lower edge corresponds to thecurvature of the openings 21 in the incubator 20. In other words, it ispossible to manufacture different types of feed funnel 30, which suitincubators 20 of different sizes, in which, however, the same type ofcuvette 70 can be used, which leads to the cost benefits sought by theinvention. Because the cuvettes 70 used in the analyser 1 are straightwhen not in use, they are economical to store.

The curvature of the side 31 of the loading device 40 receiving the feedfunnel 30 can be flat, i.e. constant, or can vary in the verticaldirection, in which case the receiving side 31 is planar on its upperedge and curves more steeply convexly when examined downwards. In thatcase, the cuvette 70 is arranged to bend in stages according to thereceiving side 31, whereas, when the side 31 is evenly curved, thecuvette 70 is arranged to bend immediately into the desired curve. Thefeed funnel 30 is also equipped with lugs on the receiving side edges,which guide the cuvette laterally. Thus, the cuvette 70 is firmly incontact through only the lugs, so that they take the wear and scratchingcaused by bending. Thus, the delicate surfaces of the cuvette 70 areprotected from wear. In addition, the side edges of the feed funnel areequipped which guides 33, which bend the cuvette into a curve. When thecuvette 70 is pressed onto the lower edge of the feed funnel 30, itslugs are pressed inwards and its partitions are bent, so that thecuvette 70 lies tightly against the receiving side 31 of the feed funnel30 and is ready to be loaded as tightly into the opening 21 of theincubator 20. With the aid of the lugs, the cuvette 70 is positioned andcentres itself into the opening 21 of the incubator 20, even though theincubator 20 may not be in precisely the correct position.

The loading device 40 comprises a vertical guide post 42, to the outeredge of which the vertically moving ram 41 is fitted. The ram 41 can bemoved, for example, by means of a vertical linear drive, or an electricmotor, to the shaft of which a toothed belt is fitted. The movement ofthe ram 41 is long enough that, when it presses the cuvette 70downwards, its upper edge is pressed into the opening 21 at the desiredheight. The vertical positioning is thus defined according to the pressdepth of the ram 41, which press depth can preferably be adjusted to besuitably programmatically, for example, by limiting the angle ofrotation of the electric motor. As above, when loading the cuvette 70into the opening 21, its lugs take most of the wear, from which itsother surfaces are protected. After the successful loading of thecuvette 70 pressed into the opening 21 in the incubator 20, the sampleto be analysed, or the reagent substance is dosed into it.

The incubator 20 is heated by electric resistances. There can also bethermal insulation around the incubator, in order to stabilize thetemperature. The heating is intended to maintain the most favourableanalysis conditions, due to which heat is conducted to the samplevessels of the cuvette 70 and from there to the samples that theycontain. For example, when analysing human samples, the targettemperature can be 37° C. However, when using cuvettes 70 of the typedescribed above, due to the partitions and lugs they contain, thereaction vessels are separated from each other and from the ends of theopenings 21, so that temperature distortions between the sample vesselsare avoided. Alternatively, the incubator 20 can also be cooled to atarget temperature, if the prevailing temperature is too high. Coolingcan be implemented using, for example, a Peltier element.

The analysis means 60 are arranged around the incubator 20, so that thecuvettes 70 need not be removed from the opening 21 during the test. Forexample, according to one preferred embodiment, the lower part of thecuvette 70 is manufactured from a clear and transparent material,through which optical tests can be performed directly, without removingthe cuvette 70 from the opening 21. Thus, the recesses of the cuvette 70loaded into an opening 21 of the incubator 20 from the loading track 50are arranged to receive substances from several manipulators, simply byaltering the position of the incubator 20. The analysis procedure canthen be arranged, for example, in such a way that the reagent is dosedinto the reaction vessel of the cuvette 70 using a reagent doser, whichtakes the substance from a reagent store. The reagent store and dosertoo are arranged around the incubator 20. Dosing of a reagent requiresthe incubator 20 to be rotated to the correct position, so that thecorrect reaction vessel of the correct cuvette 70 will be at the reagentreception position. The basic idea of the arrangement is indeed that thesample is moved in the cuvette 70 that has received it, the position ofwhich is altered by rotating the incubator 20, so that movements anddirections of movement in the analyser 1 will be as few as possible. Theanalysis means 60 can also comprise an analysis device, which sucks thesample from the reaction vessel of the cuvette 70 and measures itsproperties inside the device. A conventional analysis device like thatdescribed can be, for example, an ion-selective electrode. The samplesare analysed using an optical analysis method, for instance,photometrically.

The samples to be analysed are dosed under the same conditions as thereagent substances using a sample doser, which takes the substance froma sample store. The dosing sequence of sample and reagent substance canvary in a manner required by the tests in the analysis. The sample andreagent stores are usually carousel-type indexed stores, the storagelocations and positions of which are controlled by remote control aspart of the control of the entire analyser 1. The reagent and sample canbe mixed by rotating the incubator 20 into the vicinity of a separatemixer and starting the mixer. The content of each reaction vessel can beanalysed optically as described above and, for example, by using amanipulating analyser, which is arranged to suck the sample into itstest chamber and measure its voltage compared to a reference value. Thesetting and programming of the test periods and movements is known.There is at least one analysis station. The number and locations of theanalysis devices is limited by the number of stations that will fitaround the incubator.

In the method according to the invention, an apparatus like thatdescribed above is used by sample analysis, in which the analysis eventis controlled sample-specifically. A sample-specific and based testsequence is based on an analyser construction that permits the flexiblearrangement of the periods of the test to be performed, in such a waythat the tests required by each sample can be run one after the other asrequired. The said flexibility is based on the analysis means, substancestores, and mixers arranged around a rotatable incubator. The reactionvessel transporting the sample is then not bound to a specific path, butcan be moved to a desired station as required.

Thus, a sample is dosed into the analyser's 1 reaction vessel, where itremains only for the time required for dosing, incubation, and mixing.The difference between sample and test-based analysis is shown in FIG.4. Sample-based analysis leads to a short through-put time and apossibility to change the test sequence flexibly. The changing of thetest sequence allows, for example, an urgent test to be prioritized tobe made before the analysis of the other samples, without having to waitfor the right types of test.

Once the tests for all of the sample vessels used in the cuvette 70 areready, the cuvette 70 can be removed from the opening 21, in such a waythat the ram 41 that performed loading pushes the cuvette 70 out of theopening 21 into a separate receiving trash container, or an exit opening11 in the frame 10. Alternatively, the ram 41 can load a new cuvette 70into the feed funnel 30 through the opening 21, in which case the usedcuvette 70 is pushed by a new cuvette to fall into a separate trashcontainer, or an exit opening 11 in the frame 10. Alternatively, theanalyser 1 can be constructed in such a way that the cuvettes 70 areloaded into the openings 21 from below, in which case the loading device40 with the feed funnel 30 would be arranged beneath the incubator 20.In that case, however, it would be more difficult to remove the cuvettes70 from the openings 21, due to which it is not a preferred embodimentof the invention.

In order to ensure a short throughput time and high productivity, theanalyser 1 according to the invention is also, according to onepreferred embodiment, equipped with at least one incubator 20, onereagent store and one sample store, as well as their dosers orcombinations of them, one mixer, and one optical analysis means 60.Thus, during a single test period, several operations can be performedsimultaneously on different samples. According to one embodiment, forexample during an eight-second period, one sample and one reagentsubstance can be dosed, two mixtures can be mixed, and five samples canbe analysed.

TABLE 1 Reference numbers Reference number Component 10 frame 11 exitopening 20 incubator 21 opening 30 feed funnel 31 surface receiving thecuvette 32 side edge 33 guide 40 loading device 41 ram 42 guide post 50loading track 60 analysis means 70 cuvette

1. Chemical analyser (1), which comprises: a rotatable incubator (20),in which there are openings (21) for receiving cuvettes (70); analysismeans (60) arranged around the incubator (20); a loading device (40) forloading cuvettes (70) into the openings (21), characterized in that theopenings (21) in the incubator (20) are curved, and that the loadingdevice (40) comprises a feed funnel (30), which is arranged to bend astraight cuvette (70) to fit the opening (21), and a ram (41), which isarranged to load a cuvette (70) into an opening (21) in the incubator(20) through the feed funnel (30).
 2. Analyser (1) according to claim 1,characterized in that at least some of the analysis means (60) arearranged to analyse the samples when they are in a cuvette.
 3. Analyser(1) according to claim 1, characterized in that the analyser furthercomprises a loading track (50), which carries the cuvettes (70). 4.Analyser (1) according to claim 1, characterized in that there is aloading track (50) in it, which has a U-shaped cross-section. 5.Analyser (1) according to claim 1, characterized in that the frame (10)is equipped with an exit opening (11), which is arranged to receive acuvette (70) removed from an opening (21).
 6. Analyser (1) according toclaim 1, characterized in that the analyser (1) further comprisesreagent-substance dosing means, for dosing reagent substances into thesample vessels.
 7. Analyser (1) according to claim 1, characterized inthat the analyser (1) further comprises sample-dosing means, for dosingsamples in the sample vessels.
 8. Analyser (1) according to claim 1,characterized in that the analyser (1) further comprises a reagentstore, which is at most at the distance of the operating reach of thereagent-substance dosing means from the incubator (20).
 9. Analyser (1)according to claim 1, characterized in that the analyser (1) furthercomprises a sample store, which is at most at the distance of theoperating reach of the sample-dosing means from the incubator (20). 10.Method for analysing samples on a sample basis, in which method: areaction vessel is loaded into an opening (21) in the incubator (20); areagent and a sample are dosed into the reaction vessel and mixed; thesample is measured; and the reaction vessel is removed from theincubator (20), characterized in that the analysis sequence isdetermined sample-specifically; a cuvette (70), which comprises morethan one reaction vessel, is loaded into the incubator (20) by shapingit (70) with the aid of a feed funnel (30) to fit the curved opening(21) in the incubator (20); at least one sample in the cuvette (70) isanalysed optically when it is in the sample chamber.
 11. Methodaccording to claim 10 characterized in that a reagent substance is dosedinto the reaction vessel of the cuvette (70).
 12. Method according toclaim 10 characterized in that the sample is analysed using an opticalmethod.
 13. Device for handling cuvettes (70), which device comprises: arotatable incubator (20), in which there is at least one curved opening(21) for receiving and transporting a cuvette (70); a loading device(40), which comprises a loading track (50) for storing empty straightcuvettes (70) and transporting them to the incubator (20), as well as aram (41), which is arranged to push a cuvette (70) at the end of theloading track (50) next to the incubator (20) into an opening (21) inthe incubator (20), characterized in that the loading device (40)further comprises a feed funnel (30), which is arranged to receive astraight cuvette (70) pushed by the ram (41) and to bend it to be ableto be pushed into the curved opening (21) in the incubator (20). 14.Device according to claim 13, characterized in that the ram (41) of theloading device (40) is arranged to push the cuvette (70) through thefeed funnel (30) in a single movement.
 15. Device according to claim 13,characterized in that the ram (41) of the loading device (40) isarranged to push a used cuvette (70) out of the opening (21) in theincubator (20).
 16. Device according to claim 15, characterized in thatthe ram (41) of the loading device (40) is arranged to push the usedcuvette (70) out of the opening (21) in the incubator (20) by loading anew cuvette (70) in its place, so that this displaces the used cuvette(70).
 17. Device according to claim 13, characterized in that the feedfunnel (30) is fitted between the ram (41) and the incubator (20). 18.Device according to claim 13, characterized in that the feed funnel's(30) surface (31) receiving the cuvette (70) is evenly curved, whichcurvature corresponds to the curvature of the opening (21) in theincubator (20).
 19. Device according to claim 13, characterized in thatthe feed funnel's (30) surface (31) receiving the cuvette (70) is moresteeply curved in the direction of the opening (21) in the incubator(20), in such a way that the receiving surface (31) corresponds to thecurvature of the opening (21) at the opening (21) end.
 20. Loadingmethod for loading a cuvette (70) into an opening (21) in an incubator(20), in which method: the cuvette (70) is transported to the positionof the opening (21) in the incubator (20); the cuvette (70) is loadedinto the opening (21) in the incubator (20) by moving a ram (41),characterized in that the cuvette (70) is shaped to fit the opening (21)in the incubator (20) by using the ram (41) to load it through a curvedfeed funnel (30).